治疗中枢神经系统退行性疾病药物文档资料.pptVIP

* Agents for Parkinson’s Disease 治疗中枢神经系统退行性疾病药物 17 Parkinson’s Disease（PD） : Originally described in 1817 by British physician, James Parkinson, who called it “the shaking palsy.About 1960 the disease was traced to the loss of dopamine-producing neurons in the substantia nigra Symptoms of PD: Trembling of hands, arms, legs, jaw and face Stiffness of the arms, legs and trunk Slowness of movement Poor balance and coordination 第1节 抗帕金森氏病药 Anti-PD Drugs 1. Mechanism of PD Dopamine：Inhibition ACh: Excitation +DA Anti-Ach Stimulate D-R Slow Fast L-aminoacid transporter on BBB? D1-3, which is important for PD? 二、拟多巴胺类药物 LEVODOPA Aromatic L-amino acid decarboxylase （AADC) Active Into Blood Dopmine BBB Active CNS Dopamine ( inside or outside of C?) Carbidopa Benserazide 帕金宁, 心宁美 Indications of L-Dopa All types of PD, except for those induced by Chlorpromazine Antagonist of D2 D2 is responsible for PD Side Effects of Levodopa 1. Gastrointestinal Effects Direct stimulation Stimualtion of the chemoreceptor trigger zone located in the brainstem by DA Domperidone (吗叮啉）- Antagonist of D2 To increase the dose slowly 2. Cardiovascular Effects Increased catecholamine formation-cardiac arrhythmia Beta antagonist Long Periods Dyskinesia: A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements, similar to tics or chorea . 为什么初期治疗没有？ 2. On-off response 3. Adverse mental effects Drug Interactions Vitamin B6: A water-soluble vitamin and is part of the vitamin B complex group. Pyridoxal phosphate (PLP) is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation. PLP also is necessary for the enzymatic reaction governing the release of glucose from glycogen. *